Exploiting endocytosis for transfection of mRNA for cytoplasmatic delivery using cationic gold nanoparticles
Gustà, Muriel F. (Institut Català de Nanociència i Nanotecnologia)
Edel, Michael J. (Universitat Autònoma de Barcelona)
Salazar Montoya, Vivian Angélica (Institut Català de Nanociència i Nanotecnologia)
Alvarez-Palomo, Belén (Banc de Sang i Teixits)
Juan, Manel (Hospital Clínic i Provincial de Barcelona)
Broggini, Massimo (IRCCS-Istituto di Ricerche Farmacologiche Mario Negri)
Damia, Giovanna (IRCCS-Istituto di Ricerche Farmacologiche Mario Negri)
Bigini, Paolo (IRCCS-Istituto di Ricerche Farmacologiche Mario Negri)
Corbelli, Alessandro (IRCCS-Istituto di Ricerche Farmacologiche Mario Negri)
Fiordaliso, Fabio (IRCCS-Istituto di Ricerche Farmacologiche Mario Negri)
Barbul, Alexander (Tel Aviv University)
Korenstein, Rafi (Tel Aviv University)
Bastús, Neus G (Institut Català de Nanociència i Nanotecnologia)
Puntes, Víctor (Institut Català de Nanociència i Nanotecnologia)

Date:	2023
Abstract:	Gene therapy holds promise to cure various diseases at the fundamental level. For that, efficient carriers are needed for successful gene delivery. Synthetic 'non-viral' vectors, as cationic polymers, are quickly gaining popularity as efficient vectors for transmitting genes. However, they suffer from high toxicity associated with the permeation and poration of the cell membrane. This toxic aspect can be eliminated by nanoconjugation. Still, results suggest that optimising the oligonucleotide complexation, ultimately determined by the size and charge of the nanovector, is not the only barrier to efficient gene delivery. We herein develop a comprehensive nanovector catalogue comprising different sizes of Au NPs functionalized with two different cationic molecules and further loaded with mRNA for its delivery inside the cell. Tested nanovectors showed safe and sustained transfection efficiencies over 7 days, where 50 nm Au NPs displayed the highest transfection rates. Remarkably, protein expression was increased when nanovector transfection was performed combined with chloroquine. Cytotoxicity and risk assessment demonstrated that nanovectors are safe, ascribed to lesser cellular damage due to their internalization and delivery via endocytosis. Obtained results may pave the way to design advanced and efficient gene therapies for safely transferring oligonucleotides.
Grants:	Agencia Estatal de Investigación RTI2018-099965-B-I00 Agencia Estatal de Investigación PCI2019-103436 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-1431 Ministerio de Economía y Competitividad SEV-2017-0706
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Gold nanoparticles ; Cationic ; Transfection ; Gene therapeutics ; Safety
Published in:	Frontiers in immunology, Vol. 14 (May 2023) , art. 1128582, ISSN 1664-3224

DOI: 10.3389/fimmu.2023.1128582
PMID: 37228592

13 p, 10.6 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Experimental sciences > Catalan Institute of Nanoscience and Nanotechnology (ICN2)
Articles > Research articles
Articles > Published articles